Valve assembly with directional flow path

ABSTRACT

A valve assembly with a multidirectional flow path includes a valve body that includes respective hinged portions defining respective passageways extending through the valve body when in a closed state. A flexible conduit or tubing having a loop portion and a plurality of branches extending from the loop portion is at least partially positioned within the valve body. Portions of the loop that extend beyond the valve body are encapsulated by respective rigid jackets. Multiple valves are situated on the valve body and are used to selectively pinch the loop portion in different pinching configurations to direct fluid to or from the particular branches. The valve assembly may be integrated into a manufacturing or other production process with optional additional jackets used to encapsulate the flexible conduit branches.

RELATED APPLICATION

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/236,007 filed on Oct. 1, 2015, which is hereby incorporated byreference in its entirety. Priority is claimed pursuant to 35 U.S.C. §119 and any other applicable statute.

FIELD OF THE INVENTION

The field of the invention generally relates to valve systems used inconnection with pharmaceutical or bioprocess applications. Morespecifically, the field of the invention relates to valve systems thatincorporate flexible, sterile conduits or tubing that may be used inpharmaceutical or bioprocess applications. The valve assembly describedherein has particular suitability for use with chromatography,filtering, or trapping applications that utilize flow reversal.

BACKGROUND

Many commercial products are produced using chemical as well asbiological processes. Pharmaceuticals, for example, are produced incommercial quantities using scaled-up reactors and other equipment.So-called biologics are drugs or other compounds that are produced orisolated from living entities such as cells or tissue. Biologics can becomposed of proteins, nucleic acids, or complex combinations of thesesubstances. They may even include living entities such as cells. Inorder to produce biologics on a commercial scale, sophisticated andexpensive equipment is needed. In both pharmaceutical and biologics, forexample, various processes need to occur before the final product isobtained. For example, in the case of biologics, cells may be grown in agrowth chamber or the like and nutrients may need to be carefullymodulated into the growth chamber. Waste products produced by cells mayalso have to be removed on a controlled basis from the fermentationchamber. As another example, biologic products produced by living cellsor other organisms may need to be extracted and concentrated. Thisprocess may involve a variety of filtration and separation techniques.

Because there are a number of individual processes required to beproduce the final product, various reactants, solutions, and washes areoften pumped or otherwise transported to various subsystems usingconduits and associated valves. These systems may be quite cumbersomeand organizationally complex due to the large numbers of conduits,valves, sensors, and the like that may be needed in such systems. Notonly are these systems visually complex (e.g., resembling spaghetti)they also include many components that are required to be sterilizedbetween uses to avoid cross-contamination issues. Indeed, the case ofdrug and biologic preparation, the Federal Food and Drug Administration(FDA) is becoming increasingly strict on cleaning, sterilization orbio-burden reduction procedures that are required for drug andpharmaceutical preparations. This is particularly a concern because manyof these products are produced in batches which would require repeatedcleaning, sterilization or bio-burden reduction activities on a varietyof components.

More recently, disposable solutions have been proposed that utilizeflexible (e.g., silicone) tubing during the manufacturing process. Theflexible tubing may be discarded after use and replaced with new tubing,thereby avoiding the need to sterilize some or all of the equipment. Forvalve operations, the flexible tubing is placed inside a two-piece valveand a valve actuator is used to selectively pinch the flexible tubing.The valve is closed when the flexible tubing is pinched shut by thevalve actuator and open when the actuator leaves the flexible tubing inthe resting, open state. Often these valves need to interface with orconnect to other process operations. In many pharmaceutical orbioprocess applications, particular process operations may require thatfluid flow be reversed. In such situations, like when a chromatographycolumn is used, this may require a large number of separate valves andconduits to accomplish the desired flow reversal. There thus is a needfor a more elegant and compact solution to reverse flow that alsoincorporates the benefits of using flexible, disposable tubing.

SUMMARY

In one embodiment, a valve assembly with a multidirectional flow pathincludes a valve body that includes respective hinged portions definingrespective passageways extending through the valve body when in a closedstate. A flexible conduit or tubing having a loop portion and aplurality of branches extending from the loop portion is at leastpartially positioned within the valve body. In some embodiments, theloop portion is entirely contained within the valve body. Forembodiments in which the loop extends beyond the valve body, theseportions are encapsulated by respective rigid jackets. Multiple valvesare situated on the valve body and are used to selectively pinch theloop portion in different pinching configurations to direct fluid to orfrom the particular branches. The valve assembly may be integrated intoa manufacturing or other production process with optional additionaljackets used to encapsulate the flexible conduit branches.

In another embodiment, a valve assembly with a multidirectional flowpath includes a valve body having a first body portion (e.g., half) anda second body portion (e.g., half) connected to one another at one ormore hinges, the first body portion and the second body portion definingrespective passageways extending through the valve body when in a closedstate. A flexible conduit is disposed in the passageways of the valvebody. The flexible conduit has a loop or loop portion connected to afirst branch, a second branch, a third branch, and a fourth branch,wherein the second and fourth branches are fluidically connected to oneanother across the loop portion via a connector segment (used asbypass). A first valve is disposed on the valve body and has an actuatorconfigured to actuate a pinching element to pinch the flexible conduitloop between the first branch and the second branch. A second valve isdisposed on the valve body and has an actuator configured to actuate apinching element to pinch the flexible conduit loop between the secondbranch and the third branch. A third valve is disposed on the valve bodyand has an actuator configured to actuate a pinching element to pinchthe flexible conduit loop between the third branch and the fourthbranch. A fourth valve is disposed on the valve body and has an actuatorconfigured to actuate a pinching element to pinch the flexible conduitloop between the fourth branch and the first branch. A fifth valve isdisposed on the valve body and has an actuator configured to actuate apinching element to pinch the flexible conduit in the connector segment(e.g., the bypass segment). In this embodiment, a first portion of theloop extends outside the valve body and is contained in a first rigidjacket and a second portion of the loop extends outside the valve bodyand is contained in a second rigid jacket. The valve assembly mayinclude at least one fastener thereon to secure the valve body in aclosed state.

In another embodiment, a valve assembly with a multidirectional flowpath includes a valve body having a first body portion (e.g., half) anda second body portion (e.g., half) connected to one another at one ormore hinges, the first body portion and the second body portion definingrespective passageways extending through the valve body when in a closedstate. A flexible conduit is disposed in the passageways of the valvebody. The flexible conduit has a loop or loop portion that is containedwithin the valve body and connected to a first branch, a second branch,a third branch, and a fourth branch, wherein the second and fourthbranches are fluidically connected to one another across the loopportion via a connector segment. A first valve is disposed on the valvebody and has an actuator configured to actuate a pinching element topinch the flexible conduit loop between the first branch and the secondbranch. A second valve is disposed on the valve body and has an actuatorconfigured to actuate a pinching element to pinch the flexible conduitloop between the first branch and the second branch. A third valve isdisposed on the valve body and has an actuator configured to actuate apinching element to pinch the flexible conduit loop between the secondbranch and the third branch. A fourth valve is disposed on the valvebody and has an actuator configured to actuate a pinching element topinch the flexible conduit loop between the second branch and the thirdbranch. A fifth valve is disposed on the valve body and has an actuatorconfigured to actuate a pinching element to pinch the flexible conduitloop between the third branch and the fourth branch. A sixth valve isdisposed on the valve body and has an actuator configured to actuate apinching element to pinch the flexible conduit loop between the thirdbranch and the fourth branch. A seventh valve is disposed on the valvebody and has an actuator configured to actuate a pinching element topinch the flexible conduit loop between the fourth branch and the firstbranch. An eighth valve is disposed on the valve body and has anactuator configured to actuate a pinching element to pinch the flexibleconduit loop between the fourth branch and the first branch. A ninthvalve is disposed on the valve body and has an actuator configured toactuate a pinching element to pinch the flexible conduit in theconnector segment (e.g., bypass segment). The valve assembly includesleast one fastener configured to secure the valve body in a closedstate.

In another embodiment, a flexible conduit or tubing for use in amultidirectional flow path includes a loop having a first branch, asecond branch, a third branch, and a fourth branch, wherein the secondand fourth branches are fluidically connected to one another across theloop portion via a connector segment, wherein the loop is formed inthree (3) pieces connected at four (4) interface locations. Theinterface locations may be formed by overmolding a connector such as abubble connector at the interface locations. In one embodiment, thethree (3) pieces include a central double cross piece bonded to two TEEpieces at four (4) interface locations.

In another embodiment, a method of making a flexible conduit having aloop portion includes the steps or operations of providing a doublecross shaped section of tubing; providing a first TEE section of tubingand a second TEE section of tubing; securing one end of the first TEEsection to the double cross shaped section of tubing via a firstovermolded connector; securing one end of the second TEE section to thedouble cross shaped section of tubing via a second overmolded connector;securing a second end of the first TEE section to the double crossshaped section of tubing via a third overmolded connector; and securinga second end of the second TEE section to the double cross shapedsection of tubing via a fourth overmolded connector.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a perspective view of the valve assembly according toone embodiment.

FIG. 2 illustrates a bottom view of the valve assembly of FIG. 1.

FIG. 3 illustrates a top view of the valve assembly of FIG. 1.

FIG. 4 illustrates a bottom view of the valve assembly of FIG. 1 withone half of the valve body removed to illustrate the flexible conduittherein. Also removed in this view are respective halves of the rigidjackets.

FIG. 5 illustrates a perspective view of the valve assembly of FIG. 1with one half of the valve body removed (as well as flexible conduitremoved).

FIG. 6 illustrates a perspective of the other half removed from FIG. 5.

FIG. 7A illustrates a flexible conduit according to one embodiment.

FIGS. 7B-7F illustrate one method of making a flexible conduit having aloop portion therein.

FIG. 8 illustrates a rigid jacket according to one embodiment.

FIG. 9 illustrates how the actuator and pinching element toggles betweenclosed and open states in response to movement of the pinching element.

FIG. 10 illustrates a piping and instrumentation drawing for use of thevalve assembly in connection with a chromatography column.

FIG. 11 illustrates the valve assembly used in an exemplary highpressure application that uses a number of jackets to encapsulate theflexible conduit.

FIG. 12A illustrates another embodiment of a valve assembly thatcompletely encapsulates the loop portion of the flexible conduit in thevalve body. The valve body is illustrated in a closed state.

FIG. 12B illustrates another embodiment of a valve assembly thatcompletely encapsulates the loop portion of the flexible conduit in thevalve body. The valve body is illustrated in an open state.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

FIGS. 1-10 illustrate one embodiment of a valve assembly 10 that is usedto create a multidirectional flow path according to one embodiment. Thevalve assembly 10 includes a valve body 12 that includes a first bodyportion 14 and second body portion 16 that are connected to one anothervia one or more hinges 18 (seen in FIGS. 2, 3, 4, 5, 6). The valve body12 and the respective portions 14, 16 are typically made from a metallicmaterial (e.g., stainless steel) but it could also be formed from asuitably hard plastic material. The first and second body portions 14,16 when in a closed state, define passageways 20 (best seen in FIGS. 5and 6) that extend through the closed valve body 12 that receives theflexible conduit 70. In one embodiment the passageways 20 aresubstantially circular in cross section when the valve body 12 is in theclosed state. For example, the first body portion 14 may include asemi-annular or semi-circular passageway formed in a surface thereofthat mates with a corresponding semi-annular or semi-circular passagewayformed in a surface of the second body portion 16 to create the annularor circular passageway 20. While a circular shaped passageway 20 ispreferred other shapes could also be utilized. The particular layout ofthe passageways 20 are formed to accommodate a flexible tubing orconduit 70 that is placed therein. The size and shape of the passageways20 are such that the flexible conduit 70 fits snuggly therein. Forexample, the inner diameter of the passageways 20 may closely match theouter diameter of the flexible conduit 20. The flexible tubing orconduit 70, as disclosed below in more detail below, includes a loopportion 72 that is utilized to create a multidirectional flow path whenused in combination with a series of valves as described herein. Theflexible conduit 70 includes an internal lumen 71 (seen in FIG. 1)through which fluid travels.

The first and second body portions 14, 16 may be secured in the closedstate using one or more fasteners 22. The fasteners 22 may include apivoting latch 24 that has threads on which a knob 26 rotates that canbe tightened and/or loosened to selectively close/open the valve body12. The pivoting latch 24 may be rotated into a notch 25 or the like(see FIGS. 1 and 5) located on the first and second body portions 14, 16and the knob 26 is tightened to maintain the valve body 12 in the closedstate. Conversely, the knob 26 can be loosened and the pivoting latch 24rotated out from the notch 25 to enable the valve body 12 to be openedvia the one or more hinges 18.

Referring to FIGS. 1-4 and 7A and 7F, the flexible conduit 70 used inthis embodiment includes a loop portion 72 that defines a circular fluidpathway. Fluidly connected to the loop portion 72, in this embodiment,are a first branch 74, a second branch 76, a third branch 78, and fourthbranch 80. The flexible conduit 70 includes a connector segment 82 thatfluidically connects opposing sides of the loop portion 72. Theconnector segment 82 is used to form a bypass pathway between branches76, 78. This connector segment 82 may be located between the secondbranch 76 and the fourth branch 80 but it also may connect indirectlywith branches 76, 80 via the loop. The key requirement is that theconnector segment 82 be located in the loop portion 72 that is insidethe closure points described below.

The flexible conduit 70 is used to carry a fluid through the valveassembly 10. In the illustrated embodiment, the flexible conduit 70carries a pressurized fluid, for example, a fluid at pressures above 50psig. The flexible conduit 70 may include silicone (e.g., platinum curedsilicone) however other materials may be used. These include, forexample, a polymer such as thermoplastic elastomers (TPE), thermoplasticrubber (TPR), or the like. The flexible conduit 70 may be unreinforcedas illustrated or in some embodiments it may be reinforced. Theembodiment described herein has particular applicability forunreinforced flexible conduit 70. The flexible conduit 70 may have avariety of sizes. For example, without limiting the invention, theflexible conduit 70 may have an internal diameter of 0.5 inches and anouter diameter of 0.75 inches. Of course, this is only illustrative andother diameters may also be used.

In FIG. 7A, the ends of the first branch 74, second branch 76, thirdbranch 78, and fourth branch 80 are illustrated as relatively shortsegments but it should be understood that these branches 74, 76, 78, and80 may be longer (or shorter). In addition, the ends of the branches 74,76, 78, and 80 may terminate in a flange or the like such that anothersegment (not illustrated) may be coupled to the end of the branch 74,76, 78, and 80 using a connector or the like. The first branch 74,second branch 76, third branch 78, and fourth branch 80 may extend somedistance beyond the valve assembly 10 and may be encapsulated orenclosed in one or more jackets 120 as illustrated in FIG. 11. Thejackets 120 may include two-piece jackets that are attached to oneanother via hinges or the like. The jackets 120 may be closed around theflexible conduit or tubing 70 and secured in the closed state using oneor more fasteners like those disclosed herein to prevent the flexibleconduit 70 from expanding and failing under high fluidic pressures. Thejackets 120 may also be used to direct the flexible conduit or tubing 70to adjacent components or operations that are part of the manufacturingprocess. The jackets 120 provide the ability to direct the flexibleconduit or tubing 70 in three-dimensional space to orderly arrange andmanage the manufacturing or production process that employs flexibleconduit or tubing 70.

With reference to FIGS. 7A-7F, in one embodiment, the loop portion 72 ofthe flexible conduit 70 may be formed by joining multiple differentsegments of flexible conduit 70 to form the final structure illustratedin FIG. 7A. In this example, three different pieces or sections offlexible conduit 70 are bonded or otherwise secured to one another in amolding process to form the completed loop portion 72. For example, inone embodiment, a double cross segment 84 may be bonded to two “Y” orTEE segments 86′, 86″ using over-molded bubble connectors 88 a, 88 b, 88c, 88 d that connect the respective ends of the TEE segments 86′, 86″ tothe double cross segment 84 that is formed during the process of formingthe flexible conduit 70. In this embodiment, there are four (4)interface locations (i.e., bubble connectors 88 a, 88 b, 88 c, 88 d)that are formed where the two Y or TEE segments 86′, 86″ are secured tothe ends of the cross segment 84. Note that in other embodiments, theloop or loop portion 72 may have additional branches formed beyond thefour branches 74, 76, 78, 80 that are illustrated.

To form the flexible conduit 70 with the loop portion 72, a first Y orTEE segment 86′ is secured to the double cross segment 84 as illustratedin FIG. 7B. A mandrel 90 which may be a metallic shaft or the likehaving an outer diameter around the same as the inner diameter of theflexible tubing forming the double cross segment 84 and the Y or TEEsegment 86′ is inserted as illustrated. The joined structure is thenplaced into a mold (not shown) that includes a cavity that defines thebubble connector 88 a. A polymer material such as silicone is theninjected into the mold and cured (e.g., platinum cured) to form thebubble connector 88 a at the interface between the first Y or TEEsegment 86′ and the double cross segment 84. The mandrel 90 can then beremoved by pulling the mandrel 90 out of the now-formed structure in thedirection of arrow A in FIG. 7B. Next, with reference to FIG. 7C, asecond Y or TEE segment 86″ is secured to the double cross segment 84.The mandrel 90 in inserted into the second Y or TEE segment 86″ and thedouble cross segment 84. The joined structure is then placed into themold as described previously where a bubble connector 88 b is formedaround the joint between the second Y or TEE segment 86″ and the doublecross segment 84 as illustrated in FIG. 7C. After curing, the mandrel 90is removed by pulling the same in the direction of arrow B.

Next, with reference to FIG. 7D, the mandrel 90 is positioned within asegment or leg of the first Y or TEE segment 86′ and the double crosssegment 84 as illustrated. The joined structure is then placed into themold as described previously where a bubble connector 88 c is formedaround the joint between the second Y or TEE segment 86″ and the doublecross segment 84 as illustrated in FIG. 7C. After curing, the mandrel 90is removed by pulling the same in the direction of arrow C. Withreference to FIG. 7E, the mandrel 90 is then positioned in the remainingsegment or leg of the second Y or TEE segment 86″ and the double crosssegment 84 as illustrated. The joined structure is then placed into themold as described previously where a bubble connector 88 d is formedaround the joint between the second Y or TEE segment 86″ and the doublecross segment 84. After curing, the mandrel 90 is removed by pulling thesame in the direction of arrow D. Note that, alternatively, the segmentor leg of the second Y or TEE segment 86″ could be joined to the doublecross segment 84 prior to joining the segment or leg of the first Y orTEE segment 86′ to the double cross segment 84.

FIG. 7F illustrates a view of the completed flexible conduit 70 with theloop portion 72. Note that there are four branches 74, 76, 78, 80 orends that extend from the loop portion 72. These branches 74, 76, 78, 80may have a variety of lengths. In addition, the branches 74, 76, 78, 80of the flexible conduit 70 may have one or more optional ends orconnectors (not shown) added. These may be added via another moldingoperation. These may include extensions of clear tubing, braided hose,hose barb, or molded tri-clamp gaskets.

A significant benefit of making the flexible conduit 70 with the loopportion 72 in this manner is that valve closure points 92 a, 92 b, 92 c,92 d, 92 e, 92 f, 92 g, 92 h, 92 i can be situated at locations thateliminate or significantly reduce any hold up volumes with the loopportion 72. Other manufacturing processes apply bulky or bulbousovermolding connectors between various intersection pathways. Valveclosure points 92 a, 92 b, 92 c, 92 d, 92 e, 92 f, 92 g, 92 h, 92 icannot be located where these large overmolding features are located. Incontrast, as seen in FIG. 7F, valve closure points 92 a, 92 b, 92 c, 92d, 92 e, 92 f, 92 g, 92 h, 92 i can be located very close tointersecting fluid pathways. Importantly, these valve closure points 92a, 92 b, 92 c, 92 d, 92 e, 92 f, 92 g, 92 h, 92 i are all located atpositions where there is native flexible conduit 70 that is not overlaidor obstructed with any overmolding or other bulky joint material.

Preferably the closure points 92 a, 92 b, 92 c, 92 d, 92 e, 92 f, 92 g,92 h, 92 i are within less than 1 cm from an intersecting or adjacentflow path or fluid pathway. Even more preferably the closure points 92a, 92 b, 92 c, 92 d, 92 e, 92 f, 92 g, 92 h, 92 i are located as closeas possible to an intersecting or adjacent flow path or fluid pathwaywithout intruding into or adversely affecting the other flow path orfluid pathway. For example, as seen in FIG. 7F, there are four (4) valveclosure points 92 a, 92 b, 92 c, 92 d that are created right adjacent tothe intersecting flow paths of the double cross segment 84. Closure ofthese valve closure points 92 a, 92 b, 92 c, 92 d prevents the holdup ofvaluable reagents or products in the legs or segments of the doublecross segment 84 or the first or second Y or TEE segments 86′, 86″. Forexample, for the valve assembly 10 with five (5) valves illustrated inFIGS. 1-6, the valves are positioned to create closure points 92 a, 92b, 92 c, 92 d, 92 e that are closely located near the bypass pathwayformed between branches 76, 80 and connector segment 82.

There may also be additional valve closure points 92 f, 92 g, 92 h, 92 ias illustrated in FIG. 7F. For example, in FIG. 7F, there are four (4)additional valve closure points 92 f, 92 g, 92 h, 92 i located near thelegs or segments of the Y or TEE segments 86′, 86″. These valve closurepoints 92 f, 92 g, 92 h, 92 i prevent the holdup of fluid from branches74, 78. These additional closure points 92 f, 92 g, 92 h, 92 i are used,for example, in the valve assembly of FIGS. 12A and 12B where nine (9)valves are used. The feature of being able to minimize or even eliminateholdup volume with the loop portion 72 is particularly important forpharmaceutical and biopharmaceutical applications where even smallquantities of a drug or product can represent significant dollaramounts. Moreover, the holdup volume areas can contain residual fluidand/or reagents that can contaminate or adversely affect other processestaking place in the manufacturing operation. These may, for example,affect the yield of a product.

Referring to FIGS. 1-4 and 8, the valve assembly 10, in one embodiment,includes rigid jackets 30 that encapsulate portions of the flexibleconduit 70. In particular, the rigid jackets 30 encapsulate the parts ofthe loop portion 72 that extend outside of the valve body 12. Eachjacket 30 includes a first half 32 and a second half 34 that areconnected to one another via one or more hinges 36. Like the valve body12, when the first half 32 and the second half 34 of the jacket 30 isclosed, a passageway 38 is formed inside the jackets 30 to carryportions of the flexible conduit 70. These passageways 38 aredimensioned to accommodate the flexible conduit 70 (e.g., circularshaped when fully closed). The first half 32 and the second half 34 ofeach jacket 30 contains a semi-annular or semi-circular recess that whenbrought together in the closed state forms a circular or annularpassageway 38 that accommodates the flexible conduit 70. The dimensionsof the passageway 38 is such that the flexible conduit 70 is snugglyheld therein much like the valve body 12.

In one aspect, the jackets 30 are formed from a hard, polymer basedmaterial. For example, these include polymer materials such asacrylonitrile butadiene styrene (ABS) or other engineered thermoplasticmaterials suitable for the environment or application. Examples includestandard thermoplastics and polyolefins such as polyethylene (PE) andpolypropylene (PP), polyetherimide (PEI) (e.g., ULTEM resins), aliphaticpolyamides (e.g., Nylon), polyphenylsulfone (e.g., RADEL),fluoropolymers such as polyvinylidene fluoride (PVDF) or perfluoroalkoxy(PFA), polytetrafluoroethylene (PTFE), polycarbonate (which may be morethermally resistant), polysulfone (PSU). Of course, the jackets 30 mayalso be made from a metal material (e.g., stainless steel).

In one embodiment, the jackets 30 are held or maintained in the closedstate by the valve body 12. Specifically, as seen in FIGS. 5 and 6, thefirst and second valve body portions 14, 16 may include recesses 40formed therein that receive end portions of the jackets 30 and thusclose around the exterior portion of the jackets 30 when the valve body12 is in the closed state. Alternatively, the jackets 30 may be heldclosed by one or more fasteners such as fasteners 22 described herein.The jackets 30 may also be held together using a friction fit/press fitor similar technique. In other embodiments, the ends to of the jacket 30may include a flanged end or that like that are configured to interfacewith corresponding receiving portions on the valve body 12 (or viceversa). These may include a shoulder or groove that is formed in therecess 40 that is dimensioned to receive and accommodate the flangedend. The end of the jacket 30 may include one or more protuberances suchas a posts 31 that insert into an aperture or hole 13 in the valve body12 as illustrated in FIGS. 5, 6, and 8 to aid in securing the jacket 30relative to the valve body 12.

In yet another alternative embodiment, the jackets 30 may not interfacewith the interior of the valve body 12 and may merely abut against anouter surface thereof (or be located adjacent to an edge of the valvebody 12). In still another embodiment, the jackets 30 may be omittedentirely and the valve body 12 is made larger to hold the entire loopportion 72 of the flexible conduit 70. This embodiment is illustrated inFIGS. 12A and 12B.

Referring back to FIG. 1, in this particular embodiment, there are five(5) separate valves 50, 52, 54, 56, 58 that are secured to the firstvalve body portion 14 of the valve body 12. These valves are referred toas first valve 50, second valve 52, third valve 54, fourth valve 56, andfifth valve 58. While the valves 50, 52, 54, 56, 58 are illustratedbeing secured to the first valve body portion 14, they could also besecured to the second body portion 16 or they could be located on bothportions 12, 14 (e.g., in order to provide more space between valves).As explained herein, the valves 50, 52, 54, 56, 58 are used toselectively pinch the flexible conduit 70 that is contained within thevalve body 12. In the illustrated embodiment, each valve 50, 52, 54, 56,58 is secured to the valve body 12 using a clamp 60, although the clamp60 is optional and in some other embodiments, the valves 50, 52, 54, 56,58 may be secured to the valve body 12 directly.

Each valve 50, 52, 54, 56, 58 includes an actuator 62 that includes apinching element 64 that moves in the direction of arrow A (FIG. 9) toselectively close/open the central lumen 71 of the flexible conduit 70.The actuator 62 may be moved using any number approaches. For example,the actuator 62 may be pneumatically actuated valves using air ports 66(connected to air lines; not shown). The actuator 62 may also bemanually advanced/retracted using a bonnet or the like that is rotated.The actuator 62 may also actuated using a manually-activated toggle-typemechanism that does not require rotation of a bonnet or the like. Thisenables one to rapidly switch the valve between on/off states. Theactuator 62 may also be actuated with an electrically driven motor orservo. Typically, the valves 50, 52, 54, 56, 58 are automaticallycontrolled using off-valve electronics to control the opening/closingstates. For example a solenoid located in a separate control panelassembly (not shown) is used to control air flow to the air ports 66 toturn on/off valves 50, 52, 54, 56, 58.

With reference to FIGS. 4, 5, and 10 the first valve 50 actuatespinching element 64 that passes through an aperture 65 located in thefirst valve body portion 14 to pinch the flexible conduit 70 at closurepoint #1 as seen in FIG. 4. Closure point #1 is located between thefirst branch 74 and the second branch 76. The second valve 52 actuatespinching element 64 that passes through an aperture 65 located in thefirst valve body portion 14 to pinch the flexible conduit 70 at closurepoint #2. Closure point #2 is located between the second branch 76 andthe third branch 78. The third valve 54 actuates pinching element 64that passes through an aperture 65 located in the first valve bodyportion 14 to pinch the flexible conduit 70 at closure point #3. Closurepoint #3 is located between the third branch 78 and the fourth branch80. The fourth valve 56 actuates pinching element 64 that passes throughan aperture 65 located in the first valve body portion 14 to pinch theflexible conduit 70 at closure point #4. Closure point #4 is locatedbetween the fourth branch 80 and the first branch 74. The fifth valve 58actuates pinching element 64 that passes through an aperture 65 locatedin the first valve body portion 14 to pinch the flexible conduit 70 atclosure point #5. Closure point #5 is located in the connector segment82.

FIG. 10 illustrates a piping and instrumentation drawing for using thevalve assembly 10 in connection with a chromatography column 100. Inthis embodiment, the chromatography column 100 can operate either with aforward flow or a reverse flow. With reference to the valve assembly 10of FIG. 1, the first branch 74 of the flexible conduit 70 is connectedto the inlet port connection on the chromatography column 100. The thirdbranch 78 of the flexible conduit 70 is connected to the outlet port ofthe chromatography column 100. Fluid from the pharmaceutical orbioprocess operation (e.g., feed pump and upstream instrumentation)enters the valve assembly 10 via the second branch 76 of the flexibleconduit 70 and exits the valve assembly 10 via the fourth branch 80 (seeFIG. 2) of the flexible conduit 70 (downstream (effluent)instrumentation). In FIG. 10 PY-001, PY-002, PY-003, PY-004, PY-005illustrate solenoid valves associated with each of the valves 50, 52,54, 56, 58.

During operation of the chromatography column 100 where forward flow isused such as during column packing or normal capture mode, the valves50, 52, 54, 56, 58 are in the open/closed state according to Table 1below.

TABLE 1 Forward Flow Valve State (Open/Closed) Valve 50 Open Valve 52Closed Valve 54 Open Valve 56 Closed Valve 58 Closed

During operation of the chromatography column 100 where reverse flow isused such as during column cleaning or expanded bed processes, thevalves 50, 52, 54, 56, 58 are in the open/closed state according toTable 2 below.

TABLE 2 Reverse Flow Valve State (Open/Closed) Valve 50 Closed Valve 52Open Valve 54 Closed Valve 56 Open Valve 58 Closed

During operations where the chromatography column 100 needs to bebypassed, the valves 50, 52, 54, 56, 58 are in the open/closed stateaccording to Table 3 below.

TABLE 3 Bypass Flow Valve State (Open/Closed) Valve 50 Closed Valve 52Closed Valve 54 Closed Valve 56 Closed Valve 58 Open

FIG. 11 illustrates a valve assembly 10 that is used in an exemplaryhigh pressure process. In this embodiment, the flexible tubing 70 thatis located exterior to the valve assembly 10 is itself surrounded byseparate jackets 120. The jackets 120 may be formed from first andsecond halves that surround the flexible tubing 70 and can be lockedinto place using a fastener (like those described herein with respect tothe valve assembly 10), press-fit arrangement, or the like. The jackets120 may be made from a suitably hard material such as metal or a polymermaterial (such as those described herein) to act as an exoskeleton-typestructure to contain the flexible tubing 70 and prevent an “aneurysm”like failure of the flexible tubing 70 in response to carrying highpressure fluids. The jackets 120 may be modular and connected to oneanother (or other process components) so that there are no exposedregions of flexible tubing 70. Clamps 122 (one is shown in FIG. 11) maybe used to connect adjacent jackets 120 or jackets 120 may includefittings used to connect the various components. The jackets 120 mayhave a number of sizes and shapes to orderly arrange the flexible tubing70 according to the process in which they are used.

FIGS. 12A and 12B illustrate another embodiment of a valve assembly 200.In this embodiment, the valve assembly 200 includes a valve body 202that includes a first body portion 204 and second body portion 206 thatare connected to one another via one or more hinges 208. The valve body202 and the respective portions 204, 206 are typically made from ametallic material (e.g., stainless steel) but it could also be formedfrom a suitably hard plastic material. In this embodiment, the entireloop portion 72 (FIG. 12B) of the flexible conduit 70 is containedwithin the valve body 202. Thus, in this embodiment, there are no rigidjackets that are used to encapsulate portions of the loop portion 72 ofthe flexible conduit 70. In this embodiment, the inner facing surfacesof the first body portion 204 and the second body portion 206 eachdefine respective semi-annular or semi-circular passageways that, whenbrought together in the closed state, define a passageway 209 (e.g.,circular shaped passageway) that holds the loop portion 72 of theflexible conduit 70. The valve body 202 can be secured in the closedstate using one or more fasteners 210 as described herein. The fasteners210 may include a pivoting latch 212 that has threads on which a knob214 rotates that can be tightened and/or loosened to selectivelyclose/open the valve body 202. The pivoting latch 212 may be rotatedinto a notch 216 (FIG. 12B) or the like located on the first and secondbody portions 204, 206 and the knob 214 is tightened to maintain thevalve body 202 in the closed state. Conversely, the knob 214 can beloosened and the pivoting latch 212 rotated out from the notch 216 toenable the valve body 202 to be opened via the one or more hinges 208.

In this embodiment, there are nine (9) separate valves 220, 222, 224,226, 228, 230, 232, 234, 236 that are secured to valve body 202. In theillustrated embodiment, five (5) of these valves 220, 222, 224, 226, 228are secured to the first body portion 204 while the remaining four (4)valves 230, 232, 234, 236 are secured to the second body portion 206.Each valve 220, 222, 224, 226, 228, 230, 232, 234, 236 is secured to thevalve body 202 via a clamp 238, although the clamp 238 is optional andin some other embodiments, the valves 220, 222, 224, 226, 228, 230, 232,234, 236 may be secured to the valve body 12 directly. The valves 220,222, 224, 226, 228, 230, 232, 234, 236 may any type of valve asdescribed herein and each is used to selectively pinch the flexibleconduit 70 that is contained within the valve body 202. Each valve 220,222, 224, 226, 228, 230, 232, 234, 236 includes an actuator and pinchingelement (not illustrated) as described previously herein in priorembodiments to selectively close/open the central lumen 71 of theflexible conduit 70.

In this embodiment, the valves 220, 222, 224, 226, 228, 230, 232, 234,236 are located to provide closure points as illustrated in FIG. 7F.Thus, in this embodiment, by placing the closure points 92 a, 92 b, 92c, 92 d, 92 e, 92 f, 92 g, 92 h, 92 i near intersecting flow paths inthe loop portion 72 of the flexible conduit 70 potential holdup volumeis reduced or eliminated in the legs or segments of the double crosssegment 84 or the first or second Y or TEE segments 86′, 86″ asillustrated in FIG. 7F (the volume between closure points 92 f-92 b, 92h-92 a, 92 i-92 c, 92 d-92 g can be isolated from fluid). Further, inthis embodiment, the valves 220, 222, 224, 226, 228, 230, 232, 234, 236are positioned on both sides of the valve body 202 which providesadequate room to mount the nine valves 220, 222, 224, 226, 228, 230,232, 234, 236. In this embodiment, two valves 228, 232 can be closed toisolate the flow path between the first branch 74 and the second branch76. Another two valves 222, 230 can be closed to isolate the flow pathbetween the second branch 76 and the third branch 78. Another two valves220, 234 can be closed to isolate the flow path between the third branch78 and the fourth branch 80. Another two valves 226, 236 can be closedto isolate the flow path between the fourth branch 80 and the firstbranch 74. A single valve 224 is used to close the flow path in theconnector segment 82 (e.g., bypass pathway).

One advantage of the valve assemblies 10, 200 described herein is thatthey are relatively compact and can be positioned as well as opened andclosed by hand without the need for complicated mounting structures ortooling. In addition, valve assemblies 10, 200 permit one to quicklyreplace the flexible conduit 70 with another replacement flexibleconduit 70. In applications were sterility or aseptic conditions areneeded, the flexible conduit 70 can be swapped out and replaced with anew flexible conduit 70. This can take place with quickly by opening thevalve assembly 10, 200 using the fasteners 22, 210, removing the old ordisposable flexible conduit 70 and inserting a new flexible conduit 70into the valve assembly 10, 200 and closing the valve assembly 10, 200using the fasteners 22, 210. Not only is the valve assembly 10, 200relatively compact, it can optionally be used with additional jackets120 that can be used to direct and manage the flexible conduit 70 inmultiple dimensions to other process units or components.

While embodiments of the present invention have been shown anddescribed, various modifications may be made without departing from thescope of the present invention. For example, while the valve assemblies10, 200 has been described as being used in connection with achromatography column, the valve assembly 10, 200 can be used in anyapplication where flow reversal and bypass are needed. As anotherexample, while the flexible conduit 70 containing the loop portion 72 isillustrated as having four branches 74, 76, 78, 80 there could be morebranches coupled to the loop portion 72. In such a configuration therewould be additional valves added to the valve assembly. In addition,while the nine (9) valve embodiment of FIGS. 12A and 12B is illustratedcontaining the entire loop portion 72 in the valve body 202, the five(5) valve embodiment of FIGS. 1-6 could also be constructed such thatthe entire loop portion 72 is within the valve body 12 whereby therewould be no rigid jackets 30. In addition, it should be understood thatwhile various embodiments are described herein various feature of oneembodiment may be combined or used with another embodiment. That is tosay, features of one embodiment may be substituted or used in anotherembodiment. The invention, therefore, should not be limited, except tothe following claims, and their equivalents.

1-25. (canceled)
 26. A method of making a flexible conduit having a loopportion comprising: providing a double cross shaped section of tubing;providing a first Y or TEE section of tubing and a second Y or TEEsection of tubing; securing one end of the first Y or TEE section to thedouble cross shaped section of tubing via a first overmolded connector;securing one end of the second Y or TEE section to the double crossshaped section of tubing via a second overmolded connector; securing asecond end of the first Y or TEE section to the double cross shapedsection of tubing via a third overmolded connector; and securing asecond end of the second Y or TEE section to the double cross shapedsection of tubing via a fourth overmolded connector.
 27. The method ofclaim 26, wherein a mandrel is positioned inside the first Y or TEEsection and inside the double cross shaped section while forming thefirst overmolded connector in a molding operation followed by removal ofthe mandrel.
 28. The method of claim 26, wherein a mandrel is positionedinside the second Y or TEE section and inside the double cross shapedsection while forming the second overmolded connector in a moldingoperation followed by removal of the mandrel.
 29. The method of claim26, wherein a mandrel is positioned inside the first Y or TEE sectionand inside the double cross shaped section while forming the thirdovermolded connector in a molding operation followed by removal of themandrel.
 30. The method of claim 26, wherein a mandrel is positionedinside the second Y or TEE section and inside the double cross shapedsection while forming the fourth overmolded connector in a moldingoperation followed by removal of the mandrel.
 31. The method of claim26, wherein the first, second, third, and fourth overmolded connectorscomprise bubble connectors.
 32. The method of claim 26, wherein the thefirst, second, third, and fourth overmolded connectors comprisesilicone.
 33. A method of making a flexible conduit having a loopportion comprising: providing a double cross shaped section of tubing;providing a first Y or TEE section of tubing and a second Y or TEEsection of tubing; securing one end of the first Y or TEE section to thedouble cross shaped section of tubing via a first overmolded connector;securing one end of the second Y or TEE section to the double crossshaped section of tubing via a second overmolded connector; securing asecond end of the second Y or TEE section to the double cross shapedsection of tubing via a third overmolded connector; and securing asecond end of the first Y or TEE section to the double cross shapedsection of tubing via a fourth overmolded connector.
 34. The method ofclaim 33, wherein a mandrel is positioned inside the first Y or TEEsection and inside the double cross shaped section while forming thefirst overmolded connector in a molding operation followed by removal ofthe mandrel.
 35. The method of claim 33, wherein a mandrel is positionedinside the second Y or TEE section and inside the double cross shapedsection while forming the second overmolded connector in a moldingoperation followed by removal of the mandrel.
 36. The method of claim33, wherein a mandrel is positioned inside the first Y or TEE sectionand inside the double cross shaped section while forming the thirdovermolded connector in a molding operation followed by removal of themandrel.
 37. The method of claim 33, wherein a mandrel is positionedinside the second Y or TEE section and inside the double cross shapedsection while forming the fourth overmolded connector in a moldingoperation followed by removal of the mandrel.
 38. The method of claim33, wherein the first, second, third, and fourth overmolded connectorscomprise bubble connectors.
 39. The method of claim 33, wherein thefirst, second, third, and fourth overmolded connectors comprisesilicone.